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Collectively, these observations highlight a convergent pathogenic mechanism in NDDs, in which mitochondrial quality control failure, through impaired mitophagy, defective protein import, and ROS-driven dysfunction, links mitochondrial damage, mtDNA-mediated inflammation, and protein aggregation [68,69,70,71,72,73]

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K48-linked ubiquitination promotes proteasomal degradation, whereas K63-linked ubiquitination activates NLRP3 by recruiting binding partners, and deubiquitination by enzymes such as BRCA1/BRCA2-containing complex subunit 3 (BRCC3) and ubiquitin-specific protease 1 USP1/UAF1 or BRCC3 reverses this inhibition

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In clinical trials of tirzepatide, anywhere from 4% to 14% of participants reported headaches, depending on the dose